U.S. Brand Names

• Aptivus®

Generic Available

No

Pharmacologic Categories

• Antiretroviral Agent, Protease Inhibitor

Related Terms

• PNU-140690E
• TPV

Available Products

Image	Description
	Brand Name Aptivus® Strength 100 mg/mL Labeler Boehringer Ingelheim Pharmaceuticals Inc Class Rx Route oral NDC 005970002
	Brand Name Aptivus® Strength 250 mg Labeler Boehringer Ingelheim Pharmaceuticals Inc Class Rx Route oral NDC 005970003

Indications

Treatment of HIV-1 infections in combination with ritonavir and other antiretroviral agents; limited to highly treatment-experienced or multiprotease inhibitor-resistant patients.

Concurrent therapy of tipranavir/ritonavir with amiodarone, alfuzosin, cisapride, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), flecainide, lovastatin, midazolam (oral), pimozide, propafenone, quinidine, rifampin, sildenafil (for pulmonary arterial hypertension), simvastatin, St John’s wort, and triazolam; moderate-to-severe hepatic impairment (Child-Pugh class B and C)

Boxed warnings:

• Hepatotoxicity: See “Concerns related to adverse effects” below.
• Intracranial hemorrhage: See “Concerns related to adverse effects” below.

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).
• Hepatotoxicity: [U.S. Boxed Warning]: In combination with ritonavir, may cause hepatitis (including fatalities) and/or exacerbate pre-existing hepatic dysfunction (causal relationship not established); patients with chronic hepatitis B or C are at increased risk. Monitor patients closely; discontinue use if signs or symptoms of toxicity occur or if asymptomatic AST/ALT elevations >10 times upper limit of normal or AST/ALT elevations >5-10 times upper limit of normal concurrently with total bilirubin >2.5 times the upper limit of normal occur.
• Hypersensitivity reactions: Protease inhibitors have been associated with a variety of hypersensitivity events (some severe), including rash, anaphylaxis (rare), angioedema, bronchospasm, erythema multiforme, and/or Stevens-Johnson syndrome (rare). It is generally recommended to discontinue treatment if severe rash or moderate symptoms accompanied by other systemic symptoms occur.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required.
• Increased cholesterol: Increases in total cholesterol and triglycerides have been reported; screening should be done prior to therapy and periodically throughout treatment.
• Intracranial hemorrhage: [U.S. Boxed Warning]: Use in combination with ritonavir, has been associated with rare reports of fatal and nonfatal intracranial hemorrhage; causal relationship not established. Events often occurred in patients with medical conditions (eg, CNS lesions, head trauma, recent neurosurgery, coagulopathy, alcohol abuse) or concurrent therapy which may have influenced these events.
• Sulfonamide allergy: Use with caution in patients with sulfonamide allergy.

Disease-related concerns:

• Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of diabetes, DKA, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors.
• Hemophilia A or B: Use with caution in patients with hemophilia A or B; increased bleeding during protease inhibitor therapy has been reported.
• Hepatic impairment: Use with caution in patients with mild hepatic impairment; contraindicated in moderate-to-severe impairment.
• Platelet aggregation: May impair platelet aggregation, resulting in bleeding; use with caution in patients who may be at risk for increased bleeding (trauma, surgery or other medical conditions).

Concurrent drug therapy issues:

• Anticoagulants and antiplatelet agents: Coadministration may increase the risk of bleeding.
• Estrogens: Women receiving estrogen (as hormonal contraception or replacement therapy) have an increased incidence of rash. Alternative forms of contraception may be needed.
• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors and moderate CYP3A4 inducers. Concomitant use with selected major CYP3A4 substrates and strong CYP3A4 inducers is contraindicated (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
• Ritonavir: Coadministration with ritonavir is required.

Concurrent drug therapy issues:

• Vitamin E: Oral solution formulation contains vitamin E; additional vitamin E supplements should be avoided.

Special populations:

• Pediatrics: Safety and efficacy have not been established in children <2 years of age.

>10%:

• Dermatologic: Rash (children 21%; adults 3% to 10%)
• Endocrine & metabolic: Hypertriglyceridemia (>400 mg/dL: 61%), hypercholesterolemia (>300 mg/dL: 22%)
• Gastrointestinal: Diarrhea (15%)
• Hepatic: Transaminases increased (>2.5 x ULN: 26% to 32%; grade 3/4: 10% to 20%)
• Neuromuscular & skeletal: CPK increased (grade 3/4: children 11%)

2% to 10%:

• Central nervous system: Fever (6% to 8%), fatigue (6%), headache (5%)
• Endocrine & metabolic: Dehydration (2%)
• Gastrointestinal: Nausea (5% to 9%), amylase increased (grade 3: 6% to 8%), vomiting (6%), abdominal pain (4%), diarrhea (children 4%), weight loss (3%)
• Hematologic: Bleeding (children 8%), WBC decreased (grades 3: 5%), anemia (3%), neutropenia (2%)
• Hepatic: ALT increased (2%, grades 3/4: 10%), AST increased (grades 3/4: 6%), GGT increased (2%)
• Neuromuscular & skeletal: Myalgia (2%)
• Respiratory: Cough (children 6%), dyspnea (2%), epistaxis (children 4%)

<2%: Abdominal distension, anorexia, appetite decreased, diabetes mellitus, dizziness, dyspepsia, exanthem, facial wasting, flatulence, flu-like syndrome, gastroesophageal reflux, hepatic failure, hepatic steatosis, hepatitis, hyperbilirubinemia, hyperglycemia, hypersensitivity, immune reconstitution syndrome, insomnia, intracranial hemorrhage, lipase increased, lipoatrophy, lipodystrophy (acquired), lipohypertrophy, malaise, mitochondrial toxicity, muscle cramp, neuropathy (peripheral), pancreatitis, pruritus, renal insufficiency, sleep disorder, somnolence, thrombocytopenia

Drug Interactions

Abacavir: Protease Inhibitors may decrease the serum concentration of Abacavir. Risk C: Monitor therapy

Alfuzosin: Protease Inhibitors may increase the serum concentration of Alfuzosin. Risk X: Avoid combination

ALPRAZolam: Protease Inhibitors may increase the serum concentration of ALPRAZolam. Management: Concurrent use of alprazolam with indinavir is contraindicated. All patients receiving such a combination should be monitored closely for excessive response to alprazolam. Risk C: Monitor therapy

Amiodarone: Protease Inhibitors may decrease the metabolism of Amiodarone. Risk X: Avoid combination

Antacids: May decrease the absorption of Protease Inhibitors. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Limit indinavir adult dose to 600 mg every 8 hours with itraconazole or ketoconazole. With ritonavir, limit ketoconazole adult dose to 200 mg/day. Limit fluconazole, itraconazole, and ketoconazole to 200 mg (adult dose) with tipranavir/ritonavir. Risk D: Consider therapy modification

Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Calcium Channel Blockers (Dihydropyridine): Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Exceptions: Clevidipine. Risk D: Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If this combination is used, monitor for evidence of toxicity. The manufacturer of atazanavir recommends that a 50% dose reduction for diltiazem be considered. Risk D: Consider therapy modification

CarBAMazepine: May increase the metabolism of Protease Inhibitors. Protease Inhibitors may decrease the metabolism of CarBAMazepine. Risk D: Consider therapy modification

Cisapride: Protease Inhibitors may decrease the metabolism of Cisapride. The resultant increase in serum cisapride concentrations may result in QTc prolongation and malignant cardiac arrhythmias. Risk X: Avoid combination

Clarithromycin: Protease Inhibitors may diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed. Clarithromycin may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification

Contraceptives (Estrogens): May diminish the therapeutic effect of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Contraceptives (Estrogens). Management: Use of an alternative, non-hormone-based contraceptive is recommended. Risk D: Consider therapy modification

Corticosteroids (Orally Inhaled): Protease Inhibitors may decrease the metabolism of Corticosteroids (Orally Inhaled). Exceptions: Beclomethasone; Beclomethasone (Oral Inhalation); Flunisolide; Flunisolide (Oral Inhalation); Triamcinolone; Triamcinolone (Systemic, Oral Inhalation). Risk D: Consider therapy modification

CycloSPORINE: Protease Inhibitors may increase the serum concentration of CycloSPORINE. CycloSPORINE may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Protease Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Dabigatran Etexilate: P-Glycoprotein Inducers may decrease the serum concentration of Dabigatran Etexilate. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Delavirdine: Protease Inhibitors may decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

Didanosine: Tipranavir may decrease the serum concentration of Didanosine. Management: It is recommended that didanosine be administered at least 2 hours apart from tipranavir in order to minimize any potential dosage form-related interaction. Risk D: Consider therapy modification

Digoxin: Protease Inhibitors may increase the serum concentration of Digoxin. Increased serum concentrations of digoxin may increase risk of AV nodal blockade. Risk C: Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Tipranavir. Risk D: Consider therapy modification

Divalproex: Protease Inhibitors may decrease the serum concentration of Divalproex. Risk C: Monitor therapy

Efavirenz: May increase the metabolism of Protease Inhibitors. This specifically includes amprenavir, indinavir, and saquinavir. Efavirenz may increase the serum concentration of Protease Inhibitors. This specifically includes nelfinavir and ritonavir. Risk D: Consider therapy modification

Enfuvirtide: Protease Inhibitors may increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors. Risk C: Monitor therapy

Eplerenone: Protease Inhibitors may decrease the metabolism of Eplerenone. Risk C: Monitor therapy

Ergot Derivatives: Protease Inhibitors may increase the serum concentration of Ergot Derivatives. Exceptions: Cabergoline. Risk X: Avoid combination

Estrogen Derivatives: May enhance the dermatologic adverse effect of Tipranavir. The combination of tipranavir/ritonavir and ethinyl estradiol/norethindrone was associated with a high incidence of skin rash. Tipranavir may decrease the serum concentration of Estrogen Derivatives. Management: Women using hormonal contraceptives should consider alternative, non-hormonal forms of contraception. Risk D: Consider therapy modification

Etravirine: Tipranavir may decrease the serum concentration of Etravirine. Risk X: Avoid combination

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Flecainide: Tipranavir may increase the serum concentration of Flecainide. Risk X: Avoid combination

Fusidic Acid: Protease Inhibitors may decrease the metabolism of Fusidic Acid. Fusidic Acid may decrease the metabolism of Protease Inhibitors. Risk D: Consider therapy modification

Garlic: May decrease the serum concentration of Protease Inhibitors. Risk C: Monitor therapy

HMG-CoA Reductase Inhibitors: Protease Inhibitors may increase the serum concentration of HMG-CoA Reductase Inhibitors. Limited data suggest pravastatin may slightly decrease protease inhibitor concentrations. Management: Lovastatin and simvastatin are contraindicated with protease inhibitors; also, avoid rosuvastatin with indinavir. Use lowest possible HMG-CoA reductase inhibitor dose and monitor for signs of toxicity if these agents are used concomitantly. Exceptions: Fluvastatin. Risk D: Consider therapy modification

Lovastatin: Protease Inhibitors may increase the serum concentration of Lovastatin. Risk X: Avoid combination

Meperidine: Protease Inhibitors may enhance the adverse/toxic effect of Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine. Concentrations of the toxic Normeperidine metabolite may be increased. Risk D: Consider therapy modification

Methadone: Protease Inhibitors may decrease the serum concentration of Methadone. Risk C: Monitor therapy

MetroNIDAZOLE: May enhance the adverse/toxic effect of Tipranavir. Risk C: Monitor therapy

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor therapy

MetroNIDAZOLE (Topical): May enhance the adverse/toxic effect of Tipranavir. Risk C: Monitor therapy

Midazolam: Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam contraindicated with all protease inhibitors. IV midazolam contraindicated with fosamprenavir and nelfinavir; other protease inhibitors recommend caution, close monitoring, and consideration of lower IV midazolam doses with concurrent use. Risk X: Avoid combination

Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nefazodone: Protease Inhibitors may increase the serum concentration of Nefazodone. Risk C: Monitor therapy

Nevirapine: May increase the metabolism of Protease Inhibitors. Risk D: Consider therapy modification

P-Glycoprotein Substrates: P-Glycoprotein Inducers may decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

PHENobarbital: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of PHENobarbital. Risk D: Consider therapy modification

Phenytoin: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Phenytoin. Risk D: Consider therapy modification

Pimozide: Protease Inhibitors may decrease the metabolism of Pimozide. Risk X: Avoid combination

Propafenone: Tipranavir may increase the serum concentration of Propafenone. Risk X: Avoid combination

Protease Inhibitors: May increase the serum concentration of other Protease Inhibitors. Management: Atazanavir--indinavir combination contraindicated. Tipranavir/ritonavir or atazanavir/ritonavir not recommended with other protease inhibitors. Other combos may require dose changes. Risk D: Consider therapy modification

Proton Pump Inhibitors: Tipranavir may decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy

QuiNIDine: Protease Inhibitors may decrease the metabolism of QuiNIDine. Risk X: Avoid combination

Raltegravir: Tipranavir may decrease the serum concentration of Raltegravir. Risk C: Monitor therapy

Rifamycin Derivatives: Protease Inhibitors may decrease the metabolism of Rifamycin Derivatives. Specifically rifabutin. Rifamycin Derivatives may decrease the serum concentration of Protease Inhibitors. Rifampin administration should be avoided. Dosage adjustments with both rifabutin and the protease inhibitors are necessary if used together. Management: Avoid using rifampin with protease inhibitors. Rifabutin and protease inhibitor dose adjustments will likely be required when using rifabutin together with protease inhibitors; consult specific protease inhibitor(s) prescribing information. Risk D: Consider therapy modification

Sildenafil: Protease Inhibitors may increase the serum concentration of Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary arterial hypertension. Risk D: Consider therapy modification

Simvastatin: Protease Inhibitors may increase the serum concentration of Simvastatin. Risk X: Avoid combination

Sirolimus: Protease Inhibitors may increase the serum concentration of Sirolimus. Risk C: Monitor therapy

St Johns Wort: May increase the metabolism of Protease Inhibitors. Risk X: Avoid combination

St Johns Wort: May decrease the serum concentration of Tipranavir. Risk X: Avoid combination

Tacrolimus: Protease Inhibitors may decrease the metabolism of Tacrolimus. Risk D: Consider therapy modification

Tacrolimus (Systemic): Protease Inhibitors may decrease the metabolism of Tacrolimus (Systemic). Risk D: Consider therapy modification

Tacrolimus (Topical): Protease Inhibitors may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease the metabolism of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk X: Avoid combination

Temsirolimus: Protease Inhibitors may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism. Risk D: Consider therapy modification

Tenofovir: May decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Tenofovir. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Theophylline Derivatives: Protease Inhibitors may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination

TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy

TraZODone: Protease Inhibitors may increase the serum concentration of TraZODone. Risk D: Consider therapy modification

Triazolam: Protease Inhibitors may increase the serum concentration of Triazolam. Risk X: Avoid combination

Tricyclic Antidepressants: Protease Inhibitors may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Valproic Acid: Protease Inhibitors may decrease the serum concentration of Valproic Acid. Risk C: Monitor therapy

Vardenafil: Protease Inhibitors may increase the serum concentration of Vardenafil. Management: Limit vardenafil adult dose to max of 2.5 mg/72 hrs with ritonavir, atazanavir, or darunavir; limit to max adult dose of 2.5 mg/24 hrs with other protease inhibitors. Risk D: Consider therapy modification

Zidovudine: Protease Inhibitors may decrease the serum concentration of Zidovudine. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions

Ethanol: Capsules contain dehydrated alcohol 7% w/w (0.1 g per capsule)

Herb/Nutraceutical: St Johns wort may decrease the levels/effects of tipranavir/ritonavir; concurrent use is contraindicated. Vitamin E (high dose) may increase the risk of bleeding.

Dosing: Adults

HIV infection: Oral: 500 mg twice daily; Note: Coadministration with ritonavir (200 mg twice daily) is required.

Dosing: Elderly

Refer to adult dosing.

Dosing: Pediatric

HIV infection: Children ≥2 years: Oral: 14 mg/kg or 375 mg/m² (maximum: 500 mg/dose) twice daily. Note: Coadministration with ritonavir (6 mg/kg or 150 mg/m² [maximum: 200 mg/dose] twice daily) is required.

• If intolerance or toxicity develops and virus is not resistant to multiple protease inhibitors: May decrease dose to 12 mg/kg or 290 mg/m² twice daily. Note: Coadministration with ritonavir (5 mg/kg or 115 mg/m² twice daily) is required.

Dosing: Renal Impairment

No adjustment required.

Dosing: Hepatic Impairment

Mild impairment (Child-Pugh class A): No adjustment required.

Moderate-to-severe impairment (Child-Pugh class B-C): Concurrent use is contraindicated.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, soft gelatin, oral:

• Aptivus®: 250 mg [contains dehydrated ethanol 7%/capsule]

Solution, oral:

• Aptivus®: 100 mg/mL (95 mL) [contains propylene glycol, vitamin E; buttermint-butter toffee flavor]

Administration, Oral

Administer without regard to meals; coadministration with ritonavir is required

Pregnancy Risk Factor

C

Pregnancy Implications

Teratogenic effects were not observed in animal reproduction studies; fetotoxity was observed with some doses. It is not known if tipranavir crosses the human placenta. Pregnancy and protease inhibitors are both associated with an increased risk of hyperglycemia. Glucose levels should be closely monitored. Women receiving estrogen (as hormonal contraception or replacement therapy) have an increased incidence of rash. Alternative forms of contraception may be needed. The Perinatal HIV Guidelines Working Group notes there is insufficient data to recommend use during pregnancy; however, if used, tipranavir must be given with low-dose ritonavir boosting. Healthcare providers are encouraged to enroll pregnant women exposed to antiretroviral medications in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Healthcare providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation.

Lactation

Excretion in breast milk unknown/contraindicated

Breast-Feeding Considerations

In infants born to mothers who are HIV positive, HAART while breast-feeding may decrease postnatal infection. However, maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breast-feeding infants despite maternal therapy.

In the United States where formula is accessible, affordable, safe, and sustainable, complete avoidance of breast-feeding by HIV-infected women is recommended to decrease potential transmission of HIV.

Mechanism of Action

Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.

Pharmacodynamics/Kinetics

Absorption: Incomplete (percentage not established)

Distribution: V_d: 7.7-10 L

Protein binding: >99% (albumin, alpha₁-acid glycoprotein)

Metabolism: Hepatic, via CYP3A4 (minimal when coadministered with ritonavir)

Bioavailability: Not established

Half-life elimination: Children 2-<6 years of age: ~8 hours, 6-<12 years of age: ~7 hours, 12-18 years: ~5 hours; Adults: 6 hours

Time to peak, plasma: 3 hours

Excretion: Feces (82%); urine (4%); primarily as unchanged drug (when coadministered with ritonavir)

Monitoring Parameters

Viral load, CD4, serum glucose, liver function tests, bilirubin

Patient Education

You will be provided with a list of specific medications that should not be used during therapy; do not take any new prescriptions, OTC medications, or herbal products during therapy (even if they are not on the list) without consulting prescriber. This is not a cure for HIV, nor has it been found to reduce transmission of HIV; use appropriate precautions to prevent spread to other persons. Take exactly as directed with a high-fat meal. Maintain adequate hydration unless instructed to restrict fluid intake. If you miss a dose, take as soon as possible and return to your regular schedule (never take a double dose). Frequent blood tests may be required with prolonged therapy. You may be advised to check your glucose levels; this drug can cause exacerbation or new-onset diabetes. May cause body changes due to redistribution of body fat, facial atrophy, or breast enlargement (normal effects of drug). May cause dizziness, insomnia, abnormal thinking (use caution when driving or engaging in potentially hazardous tasks until response to drug is known); nausea, vomiting, or taste perversion (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); muscle weakness (consult prescriber for approved analgesic); or headache or insomnia (consult prescriber for medication). Inform prescriber if you experience muscle numbness or tingling; unresolved persistent vomiting, diarrhea, or abdominal pain; respiratory difficulty or chest pain; unusual skin rash; change in color of stool or urine; or any persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber for appropriate contraceptives. Do not breast-feed.

Dietary Considerations

Capsule contains dehydrated ethanol. Oral solution formulation contains vitamin E; additional vitamin E supplements should be avoided. May be taken without regard to meals.

Storage

Capsule: Prior to opening bottle, store under refrigeration at 2°C to 8°C (36°F to 46°F). After bottle is opened, may be stored at controlled room temperature of 25°C (77°F) for up to 60 days.

Oral solution: Store at 15°C to 30°C (59°F to 86°F). After bottle is open, use within 60 days. Do not refrigerator or freeze oral solution.

• Graff J, von Hentig N, Kuczka, K, et al, “Significant Effects of Tipranavir on Platelet Aggregation and Thromboxane B2 Formation in vitro and in vivo,” J Antimicrob Chemother, 2008, 61(2):394-9. [PMID:18156609]
• “Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Panel on Clinical Practices for Treatment of HIV Infection,” December 1, 2009. Available at http://www.aidsinfo.nih.gov.
• “Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States,” May 24, 2010. Available at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf.
• Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, “Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection,” February 23, 2009. Available at http://www.aidsinfo.nih.gov.